The objectives of this project are to develop the ability to measure peptide secretory products of the neurohypophysis in an effort to better understand the physiology of neurohypophyseal secretion and the contribution of the pathophysiology of this gland to certain disease states in man. To determine the function of this gland, we have developed the ability to assay neurophysins which are carrier proteins for the hormones oxytocin and vasopressin. We have identified a human neurophysin, nicotine-stimulated neurophysin (NSN), which appears to be associated with vasopressin and a second neurophysin, estrogen-stimulated neurophysin (ESN), which appears to be associated with oxytocin in man. During normal physiologic alterations of fluid balance in man there appears to be an association between NSN and vasopressin secretion. However, in pathologic situations this may not be so. We have identified patients with ectopic production of vasopressin, presumably by a tumor, in which the tumor did not concurrently produce NSN. The understanding of secretion of the posterior pituitary gland has been greatly enhanced by the development of the radioimmunoassay for rat neurophysin and for vasopressin. This will allow us to use this small animal for indepth studies of posterior pituitary function. We have already demonstrated a clear cut hypersecretion of vasopressin and neurophysin in rats after adrenalectomy. This undoubtedly contributes to the inability to excrete water in adrenal insufficiency. We now have the tools to study posterior pituitary function in humans and to reproduce abnormalities in an animal model. BIBLIOGRAPHIC REFERENCES: Robinson, A.G.: Isolation and secretion of individual human neurophysins, J. Clin. Invest. 55:360-367, 1975. Robinson, A.G.: Radioimmunoassay of neurophysin proteins: Utilization of specific neurophysins in vivo. Annals N.Y. Acad. Sci. 248:246, 1975.